Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Dipolar Huygens-Kerker radiation for surface waves.

Exotic dipolar radiation with zero light emission in one direction but maximal light emission in the opposite direction was envisioned by Huygens in 1690, and it could emerge in vacuum if the ratio between the source's electric and magnetic dipole moments fulfills the Kerker condition as revealed by Kerker in 1983. Due to its intricate connection with both the Huygens principle and Kerker condition, this radiation phenomenon is suggested to be termed as dipolar Huygens-Kerker radiation, and at this moment, the ratio is termed as the Huygens-Kerker ratio. However, the dipolar Huygens-Kerker radiation remains underexplored in non-vacuum matters, inside which the source locates, especially for surface waves. Here we find that the dipolar Huygens-Kerker radiation of surface waves in principle could occur in non-vacuum matters and is essentially featured with the same normalized radiation pattern, which is closely related to the inclination factor that appears in the Fresnel-Kirchhoff diffraction theory. Moreover, the corresponding Huygens-Kerker ratio is intrinsically determined by the phase velocity of excited surface waves. To be specific, the Huygens-Kerker ratio is proportional to the phase velocity for transverse-magnetic surface waves but becomes inversely proportional to the phase velocity for transverse-electric surface waves.

Near-field directionality governed by asymmetric dipole-matter interactions.

Directionally molding the near-field and far-field radiation lies at the heart of nanophotonics and is crucial for applications such as on-chip information processing and chiral quantum networks. The most fundamental model for radiating structures is a dipolar source located inside homogeneous matter. However, the influence of matter on the directionality of dipolar radiation is oftentimes overlooked, especially for the near-field radiation. As background, the dipole-matter interaction is intrinsically asymmetric and does not fulfill the duality principle, originating from the inherent asymmetry of Maxwell's equations, i.e., electric charge and current density are ubiquitous but their magnetic counterparts are non-existent to elusive. We find that the asymmetric dipole-matter interaction could offer an enticing route to reshape the directionality of not only the near-field radiation but also the far-field radiation. As an example, both the near-field and far-field radiation directionality of the Huygens dipole (located close to a dielectric-metal interface) would be reversed if the dipolar position is changed from the dielectric region to the metal region.

Forkhead box E1, frequently downregulted by promoter methylation, inhibits colorectal cancer cell growth and migration.

Forkhead box E1 (FOXE1), also known as thyroid transcription factor 2 (TTF-2), belongs to a large family of forkhead transcription factors. It plays important roles in embryogenesis, cell growth, and differentiation. Cancer-specific FOXE1 hypermethylation events have been identified in several cancers. However, the expression and function of FOXE1 in the tumorigenesis of colorectal cancer remain still unknown. In this study, we examined FOXE1 expression and methylation in normal colon mucosa, colorectal cancer (CRC) cell lines, and primary tumors by immunohistochemistry, semi-quantitative RT-PCR, methylation-specific PCR, and bisulfite genomic sequencing. We found that FOXE1 was frequently methylated and silenced in CRC cell lines and was downregulated in CRC tissues compared with paired adjacent non-tumor tissues. Meanwhile, low FOXE1 expression was significantly correlated with lymph node metastasis and advanced TNM stages, indicating its potential as a tumor marker. Subsequently, we established colon cancer cell lines with stable FOXE1 expression to observe the biological effect on colorectal cancer, including cell growth, migration, actin cytoskeleton, and growth of human colorectal xenografts in nude mice. Ectopic expression of FOXE1 could suppress tumor cell growth and migration and affect the organization of the actin cytoskeleton together with suppressing tumorigenicity in vivo. FOXE1 methylation was frequently seen in association with a complete absence of or downregulated gene expression, and FOXE1 plays a suppressive role in the development and progression of colorectal cancer.

Analysis of correlative risk factors for radiation-induced hypothyroidism in head and neck tumors.

OBJECTIVE: The aim of the study is to identify clinical and dosimetric factors that could predict the risk of radiation-induced hypothyroidism(RIHT) in head and neck cancer(HNC) patients following intensity-modulated radiotherapy(IMRT). METHODS: A total of 103 HNC patients were included in our study. General clinical characteristic and dosimetric data of all recruited patients were analyzed, respectively. The univariate and multivariate logistic regression anlalysis were successively conducted to identify optimal predictors, which aim to construct the nomogram. And the joint prediction was performed. RESULTS: The incidence of patients with HNC was 36.9% (38/103). Among the clinical factors, gender, N stage, chemotherapy, frequency of chemotherapy and surgery involving the thyroid were related to RIHT. Logistic regression analysis showed that thyroid volume, Dmean, VS45, VS50, VS60 and V30,60 were independent predictors of RIHT, which were also incorporated in the nomogram. An AUC of 0.937 (95%CI, 0.888-0.958) also was showed outstanding resolving ability of the nomogram. When the volume of the thyroid was greater than 10.6 cm3, the incidence of RIHT was 14.8%, and when the volume of the thyroid was equal to or smaller than 10.6 cm3, the incidence was 72.5%. The incidence rates of RIHT in the group with VS60≦8.4cm3 and VS60 > 8.4cm3 were 61.4% and 19.3%, respectively. CONCLUSIONS: Thyroid volume and thyroid VS60 are independent predictors of RIHT in patients with HNC. Moreover, more attention should be paid to patients with thyroid volume ≤ 10.6cm3. Thyroid VS60 > 8.4cm3 may be a useful threshold for predicting the development of RIHT. The nomogram conducted by the research may become a potential and valuable tool that could individually predict the risk of RIHT for HNC patients.

Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia.

Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10-2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10-3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10-3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.

Levosimendan Relaxes Thoracic Aortic Smooth Muscle in Mice by Inhibiting PKC and Activating Inwardly Rectifying Potassium Channels.

ABSTRACT: Studies have examined the therapeutic effect of levosimendan on cardiovascular diseases such as heart failure, perioperative cardiac surgery, and septic shock, but the specific mechanism in mice remains largely unknown. This study aimed to investigate the relaxation mechanism of levosimendan in the thoracic aorta smooth muscle of mice. Levosimendan-induced relaxation of isolated thoracic aortic rings that were precontracted with norepinephrine or KCl was recorded in an endothelium-independent manner. Vasodilatation by levosimendan was not associated with the production of the endothelial relaxation factors nitric oxide and prostaglandins. The voltage-dependent K + channel (K V ) blocker (4-aminopyridine) and selective K Ca blocker (tetraethylammonium) had no effect on thoracic aortas treated with levosimendan, indicating that K V and K Ca channels may not be involved in the levosimendan-induced relaxation mechanism. Although the inwardly rectifying K + channel (K ir ) blocker (barium chloride) and the K ATP channel blocker (glibenclamide) significantly inhibited levosimendan-induced vasodilation in the isolated thoracic aorta, barium chloride had a much stronger inhibitory effect on levosimendan-induced vasodilation than glibenclamide, suggesting that levosimendan-induced vasodilation may be mediated by K ir channels. The vasodilation effect and expression of K ir 2.1 induced by levosimendan were further enhanced by the PKC inhibitor staurosporine. Extracellular calcium influx was inhibited by levosimendan without affecting intracellular Ca 2+ levels in the isolated thoracic aorta. These results suggest that K ir channels play a more important role than K ATP channels in regulating vascular tone in larger arteries and that the activity of the K ir channel is enhanced by the PKC pathway.

The plasma-soluble CSF1R level is a promising prognostic indicator for pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Improved Water Collection from Short-Term Fog on a Patterned Surface with Interconnected Microchannels.

Fog harvesting is considered a promising freshwater collection strategy for overcoming water scarcity, because of its environmental friendliness and strong sustainability. Typically, fogging occurs briefly at night and in the early morning in most arid and semiarid regions. However, studies on water collection from short-term fog are scarce. Herein, we developed a patterned surface with highly hydrophilic interconnected microchannels on a superhydrophobic surface to improve droplet convergence driven by the Young-Laplace pressure difference. With a rationally designed surface structure, the optimized water collection rate from mild fog could reach up to 67.31 g m-2 h-1 (6.731 mg cm-2 h-1) in 6 h; this value was over 130% higher than that observed on the pristine surface. The patterned surface with interconnected microchannels significantly shortened the startup time, which was counted from the fog contact to the first droplet falling from the fog-harvesting surface. The patterned surface was also facilely prepared via a controllable strategy combining laser ablation and chemical vapor deposition. The results obtained in outdoor environments indicate that the rationally designed surface has the potential for short-term fog harvesting. This work can be considered as a meaningful attempt to address the practical issues encountered in fog-harvesting research.

The impact of climate policy uncertainty on corporate pollution Emissions--Evidence from China.

Climate change is considered one of the major systemic risks facing the world in the 21st century. To address climate change, China has adopted a series of climate policies, but the uncertainty brought about by frequent climate policy issuance has increased pressure on enterprises, which may not be conducive to enterprises reducing emissions. This paper uses data on 1211 listed companies on the A-share market in China from 2012 to 2022 to study the impact of climate policy uncertainty on enterprise pollutant emissions. The research findings show that climate policy uncertainty increases corporate pollution emissions; climate policy uncertainty mainly generates negative impacts on enterprise environmental regulation, social responsibility, and R&D investment, thereby negatively affecting enterprise emissions reduction. Further heterogeneity analysis shows that climate policy uncertainty in China has a more significant impact on non-state-owned enterprises, technology-intensive enterprises, lightly polluting enterprises, and enterprises in western regions. These findings emphasize the importance of enterprise social responsibility, environmental regulation, and R&D investment in enterprise emissions reduction and provide policy implications for Chinese enterprises to optimize their energy-saving and emission reduction strategies in the face of climate policy uncertainty.

Development of a 10-litre pilot scale micro-nano bubble (MNB)-enhanced photocatalytic system for wastewater treatment.

A 10-litre pilot scale micro-nano bubble (MNB)-enhanced photocatalytic degradation system was developed using ZnO as the photocatalyst and salicylic acid (SA) as the model pollutant. The effectiveness of the MNB/ZnO/UV system was systematically compared with those of MNB, UV, MNB/UV, MNB/ZnO and ZnO/UV degradation systems. The effects of process parameters, including catalyst dosage, pollutant concentration, air-intake rate, pH and salt content on the degradation of SA, were comprehensively investigated. Optimum performance was obtained at neutral conditions with a catalyst dosage of 0.3 g/L and an air-intake rate of 0.1 L/min. For the degradation of SA, a kinetic constant of 0.04126/min was achieved in the MNB/ZnO/UV system, which is 4.5 times greater than that obtained in the conventional ZnO/UV system. The substantial increase in the degradation rate can be attributed to that the air MNB not only enhanced the gas-liquid mass transfer efficiency but also elevated the concentration of dissolved oxygen. A 10-litre pilot scale MNB/ZnO/UV system was successfully applied to the purification of lake water and river water, demonstrating great application potential for wastewater treatment.

Impact of KRAS mutation on the tumor microenvironment in colorectal cancer.

Kirsten rat sarcoma viral oncogene homolog (KRAS) is an oncogene implicated in the pathophysiology of many cancers. Increasing evidence shows that KRAS mutation is correlated with poor prognosis in numerous cancers, including colorectal cancer (CRC), breast cancer, and melanoma. KRAS also participates in regulating the CRC microenvironment. However, the direct and indirect therapeutic targets of KRAS in CRC have not been identified; thus, elucidating the mechanisms and interactions between KRAS and the tumor microenvironment (TME) in-depth is paramount. Herein, we present some of the major roles KRAS plays in shaping the heterogeneity of the TME and propose a potential strategy for targeting the downstream components of the KRAS signaling pathway and the TME in CRC.

Effects of extreme temperatures on public sentiment in 49 Chinese cities.

The rising sentiment challenges of the metropolitan residents may be attributed to the extreme temperatures. However, nationwide real-time empirical studies that examine this claim are rare. In this research, we construct a daily extreme temperature index and sentiment metric using geotagged posts on one of China's largest social media sites, Weibo, to verify this hypothesis. We find that extreme temperatures causally decrease individuals' sentiment, and extremely low temperature may decrease more than extremely high temperature. Heterogeneity analyses reveal that individuals living in high levels of PM2.5, existing new COVID-19 diagnoses and low-disposable income cities on workdays are more vulnerable to the impact of extreme temperatures on sentiment. More importantly, the results also demonstrate that the adverse effects of extremely low temperatures on sentiment are more minor for people living in northern cities with breezes. Finally, we estimate that with a one-standard increase of extremely high (low) temperature, the sentiment decreases by approximately 0.161 (0.272) units. Employing social media to monitor public sentiment can assist policymakers in developing data-driven and evidence-based policies to alleviate the adverse impacts of extreme temperatures.

Triboelectric Nanogenerators for Preventive Health Monitoring.

With the improvement in life quality, the increased focus on health has expedited the rapid development of portable preventative-health-monitoring devices. As one of the most attractive sensing technologies, triboelectric nanogenerators (TENGs) are playing a more and more important role in wearable electronics, machinery condition monitoring, and Internet of Things (IoT) sensors. TENGs possess many advantages, such as ease of fabrication, cost-effectiveness, flexibility, material-selection variety, and the ability to collect low-frequency motion, offering a novel way to achieve health monitoring for human beings in various aspects. In this short review, we initially present the working modes of TENGs based on their applications in health monitoring. Subsequently, the applications of TENG-based preventive health monitoring are demonstrated for different abnormal conditions of human beings, including fall-down detection, respiration monitoring, fatigue monitoring, and arterial pulse monitoring for cardiovascular disease. Finally, the discussion summarizes the current limitations and future perspectives. This short review encapsulates the latest and most influential works on preventive health monitoring utilizing the triboelectric effect for human beings and provides hints and evidence for future research trends.

The health and welfare effects of environmental governance: Evidence from China.

Environmental regulations aim to reduce pollution and improve air quality and the health of residents. However, there is a lack of research focusing on the health and welfare effects of low-carbon city pilot policies. In this context, this study takes China's low-carbon city pilot policy as an entry point, focuses on the health effects of public environmental governance, and systematically investigates the effects and mechanisms of low-carbon city development on the health of middle-aged and elderly people by applying the difference-in-differences method. The study finds that low-carbon city (LCC) policy significantly improves the physical and mental health of middle-aged and elderly people, and the main transmission mechanism is the reduction in air pollution and improvement in social capital. These results hold following a series of robustness tests. Furthermore, low-carbon city construction can reduce hospitalization and outpatient costs for people over 45 years old by up to 3 % and 15.5 %, respectively. The findings of this study provide useful policy insights for ensuring sustainable improvement in environmental quality and public health.

LADRC-based grid-connected control strategy for single-phase LCL-type inverters.

To ensure that grid-connected currents are of high quality, it is crucial to optimize the dynamic performance of grid-connected inverters and their control. This study suggests using a combination of reduced-order linear active disturbance rejection control (LADRC) and a Proportional-Integral (PI) controller. By applying this control strategy to a single-phase photovoltaic grid-connected system, the system's ability to suppress grid harmonics is significantly improved. The validity and effectiveness of this control approach have been confirmed through simulations and experiments. The results show that the LADRC-based control system is robust and capable of rejecting disturbances, resulting in a significant reduction in the Total Harmonic Distortion (THD) of grid-connected currents. Comparative analysis with traditional control methods demonstrates the superior performance of the proposed approach.

Dimethyl Sulfoxide: An Ideal Electrochemical Probe for Hydroxyl Radical Detection.

In situ and real-time determination of hydroxyl radicals (•OH) in physiological and pathological processes is a great challenge due to their ultrashort lifetime. Herein, an electrochemical method was developed by using dimethyl sulfoxide (DMSO) as a trapping probe for rapid determination of •OH in aqueous solution. When DMSO reacted with •OH, an intermediate product methane sulfinic acid (MSIA) was formed, which can be electrochemically oxidized to methanesulfonic acid (MSA) on the glassy carbon electrode (GCE), resulting in a distinct voltammetric signal that is directly proportional to the concentration of •OH. Other commonly encountered reactive oxygen species (ROS), including hypochlorite anions (ClO-), superoxide anions (O2•-), sulfate radicals (SO4•-), and singlet oxygen (1O2), have showed no interference for •OH determination. Thus, an electrochemical method was developed for the determination of •OH, which exhibits a wide linear range (0.4-5120 µM) and a low limit detection of 0.13 µM (S/N = 3) and was successfully applied for the quantification of •OH in aqueous extracts of cigarette tar (ACT). Alternatively, the same reaction mechanism is also applicable for the determination of DMSO, in which a linear range of 40-320 µM and a detection limit 13.3 µM (S/N = 3) was achieved. The method was used for the evaluation of DMSO content in cell cryopreservation medium. This work demonstrated that DMSO can serve as an electrochemical probe and has valuable application potential in radical study, biological research, and environmental monitoring.

A SIMPLE, QUICK, AND ECONOMICAL METHOD FOR IN VITRO CULTIVATION OF ECHINOCOCCUS MULTILOCULARIS METACESTODE AND GENERATION OF PRIMARY CELLS.

Alveolar echinococcosis is considered to be one of the most potentially lethal parasitic zoonotic diseases. However, the molecular mechanisms by which Echinococcus multilocularis interacts with hosts are poorly understood, hindering the prevention and treatment of this disease. Due to the great advantages of cell culture systems for molecular research, numerous attempts have been made to establish primary cell cultures for E. multilocularis. In this study we developed a simple, rapid, and economical method that allows E. multilocularis metacestode tissue blocks to generate daughter vesicles without the continuous presence of host feeder cells in a regular medium. We performed anaerobic, hypoxic (1% O2), normoxic, and semi-anaerobic (in sealed tubes) cultures and found that E. multilocularis metacestode tissues can produce daughter vesicles only in the sealed tubes after 4 wk of incubation. The daughter vesicles cultivated in this system were remarkably enlarged under anaerobic conditions after 8 days of culture, whereas vesicles cultured under hypoxic (1% O2) and normoxic conditions showed only a mild increase in volume. Our in vitro cultivated vesicles showed strong viability and could be used to test antiparasitic drugs, isolate primary cells, and infect animals.

Self-encapsulated ionic fibers based on stress-induced adaptive phase transition for non-contact depth-of-field camouflage sensing.

Ionically conductive fibers have promising applications; however, complex processing techniques and poor stability limit their practicality. To overcome these challenges, we proposed a stress-induced adaptive phase transition strategy to conveniently fabricate self-encapsulated hydrogel-based ionically conductive fibers (se-HICFs). se-HICFs can be produced simply by directly stretching ionic hydrogels with ultra-stretchable networks (us-IHs) or by dip-drawing from molten us-IHs. During this process, stress facilitated the directional migration and evaporation of water molecules in us-IHs, causing a phase transition in the surface layer of ionic fibers to achieve self-encapsulation. The resulting sheath-core structure of se-HICFs enhanced mechanical strength and stability while endowing se-HICFs with powerful non-contact electrostatic induction capabilities. Mimicking nature, se-HICFs were woven into spider web structures and camouflaged in wild environments to achieve high spatiotemporal resolution 3D depth-of-field sensing for different moving media. This work opens up a convenient route to fabricate stable functionalized ionic fibers.